Central administration of vitamin B12 aggravates cataplexy in canine narcolepsy.
Experimental evidence in canine narcolepsy suggests that central cholinergic systems are critically involved in the regulation of cataplexy, an abnormal manifestation of REM sleep atonia. In the current study, we found that intracerebroventricular perfusion of methyl-B12, (10(-5)-10(-2) M), significantly aggravated cataplexy and enhanced REM sleep in narcoleptic dogs. Choline, a direct precursor of acetylcholine, was also found to aggravate cataplexy, while cyano-B12, a vitamin B12 analog without methyl donating abilities, had no effect on cataplexy. Since both methyl-B12 and choline are reported to enhance acetylcholine synthesis, enhancement of the biosynthesis of acetylcholine may be involved in the effects observed in canine narcolepsy. Our results suggest that central administration of methyl-B12 has the potential to modulate both normal and pathological REM sleep.
Honda
K
K
Sleep Disorders and Research Center, Stanford University, Palo Alto, CA 94304, USA.
Riehl
J
J
Inoué
S
S
Mignot
E
E
Nishino
S
S
D000704:Analysis of Variance; D000818:Animals; D002375:Catalepsy / Q000209:etiology*; D002552:Cerebral Ventricles; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D008297:Male; D009290:Narcolepsy / Q000150:complications*; D010477:Perfusion; D012895:Sleep, REM / Q000187:drug effects; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000494:pharmacology
C019476:mecobalamin; D014805:Vitamin B 12